The overall objective of this project is to determine the effect of age on hepatic drug metabolic dysfunction as a result of a traumatic injury. We have found using abdominal aorta ligation in rats as a suitable trauma model that both cytochrome P-450 and mixed function amine oxidase were altered. In particular, we observed that both of these enzymes, in adults, decreased rapidly within the first few hours post-traumatic unjury. Within 36 hours, the decrease was as much as 38%. After 3 days, cytochrome P-450 returned to almost normal while mixed fucntion amine oxidase remained depressed. When this same model system was used except old animals were used, we found several important observations. First, although both cytochrome P-450 and mixed function amine oxidase were depressed, the depressed level for cytochrome P-450 was double that for mixed function amine oxidase. In addition, we observed a biphasic effect on conjugation reactions. Initially, increasing the rate of conjugation and by day 3 post-injury, a depression was noted which last for an additional three days. We are presently investigating these observations using different trauma models such as soft tissue injury and broken bones.